The present meta-analysis of case-control studies showed that the relatively high serum vitamin D level was associated with the decreased risk of LTBI. The result of cohort studies suggested that the decreased incidence of LTBI was associated with the elevated serum vitamin D levels.
After entering into the human body, Mycobacterium tuberculosis will be lysed in the phagosomes inside macrophages. If the concentration of Ca2+ in cells does not increase, Mycobacterium tuberculosis resides in phagosomes are not lysed, thereby resulting in LTBI . LTBI patients may develop TB in the near or distant future . The association between vitamin D deficiency and LTBI remained unclear . However, our meta-analysis showed an association between serum vitamin D levels and LTBI. Before antibiotics, vitamin D was regularly used to treat mycobacterial diseases such as tuberculosis and leprosy . Vitamin D has been reported to induce interleukin-1-β secretion and further regulate paracrine signaling, which enhances the role of macrophages in innate immune regulation . Tung et al. reported that vitamin D improved the coordinated response of monocytes and T-lymphocytes to Mycobacterium tuberculosis in response to frequent MTB exposure . In addition, 1,25-(OH)2D has long been thought to contribute to the innate and adaptive immune defense of intracellular pathogens, although the effects of 1,25-(OH)2D on Mycobacterium tuberculosis infection are complex and have not been described in detail in previous studies [11, 33]. However, there is ample evidence that serum vitamin D levels are significantly decreased in immunocompromised individuals and tuberculosis patients . These findings may indicate that vitamin D plays a role in the prevention of Mycobacterium tuberculosis infection.
However, the hypothesis that vitamin D supplementation can prevent LTBI activation has not been systematically reviewed. This is due to the lack of relevant studies . Our study only demonstrated that higher serum vitamin D levels may be a protective factor for LTBI. Arnedo-pena et al. found that low plasma vitamin D was associated with tuberculin skin test (TST) positive conversion in a small number of contacts at follow-up . Moreover, Gibney et al. observed that higher vitamin D levels were associated with lower LTBI prevalence among sub-Saharan African migrants in Melbourne, Australia . According to previous reports, the vitamin D levels of LTBI patients were significantly lower than that of healthy people , the general population receiving vitamin D showed enhanced anti-TB immunity compared with those receiving placebo , and the TST conversion rate was lower in school children who received vitamin D, and their height increased . Only a few studies have evaluated the role of vitamin D supplementation in preventing LTBI acquisition in contacts. A randomized controlled trial (RCT) by Martineau et al. found that compared with placebo group, the innate immunity against mycobacteria in vitamin D group was significantly improved, which was shown by recombinant Mycobacterium growth restriction (BCG-lux analysis), but the parameters of acquired immune response were not improved . Thus, we can hypothesize that vitamin D may inhibit the progression from LTBI to active TB [39, 40].
One of the limitations of our study is that it is still not resolved whether vitamin D supplementation is conductive to the prevention of LITB. Previous meta-analysis found that vitamin D deficiency was associated with an increased risk of developing active TB in those subjects with LTBI and with an increased risk of TST conversion/TB infection conversion . However, the meta-analysis did not address the question of whether vitamin D supplementation would be beneficial to LTBI prevention, and our study focused on the effect of higher serum vitamin D levels relative to lower vitamin levels on LTBI, rather than merely vitamin D deficiency, which is different from the previous meta-analysis. In addition, since all the studies included in the meta-analysis were observational studies and RCTs of vitamin D supplementation were few (only two articles were retrieved), we could only acquire the relationship between serum vitamin D level (25(OH)D) and LTBI. We can only assume that vitamin D supplementation prevents the activation of latent TB, and further RCTs are needed to verify this hypothesis.